RESUMO
Mycosis fungoides (MF) is the most prevalent primary cutaneous T-cell lymphoma, with an indolent or aggressive course and poor survival. The pathogenesis of MF remains unclear, and prognostic factors in the early stages are not well-established. Here, we characterized the most recurrent genomic alterations using whole-exome sequencing of 67 samples from 48 patients from Lille University Hospital (France), including 18 sequential samples drawn across stages of the malignancy. Genomic data were analyzed on the Broad Institute's Terra bioinformatics platform. We found that gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), or mutations in JUNB and TET2 are associated with high-risk disease stages. Furthermore, gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), and del6q16.3 (TNFAIP3) are coupled with shorter survival. Del6q16.3 (TNFAIP3) was a risk factor for progression in low-risk patients. By analyzing the clonal heterogeneity and the clonal evolution of the cohort, we defined different phylogenetic pathways of the disease with acquisition of JUNB, gain10p15.1 (IL2RA and IL15RA), or del12p13.1 (CDKN1B) at progression. These results establish the genomics and clonality of MF and identify potential patients at risk of progression, independent of their clinical stage.
RESUMO
BACKGROUND: Systemic treatment options for psoriasis are limited for patients with recent neoplasia. OBJECTIVES: We report the real-life use of apremilast (APR) in patients with psoriasis and recent cancer. MATERIALS & METHODS: We conducted a retrospective, multicentre study in five hospitals and among 120 private dermatologists in the north of France from January 2015 to May 2021. We included patients treated with APR for psoriasis and suffering from an active cancer or who had been diagnosed with a cancer or treated for a cancer within the last five years. RESULTS: We included 23 patients diagnosed with a cancer, on average 2.6 years before the introduction of APR for psoriasis. In most patients, APR was specifically chosen due to oncological history. At 16±8 weeks, 55% (n=11/20) of patients had achieved PASI 50 score, 30% (n=6/20) PASI 75, 5% (n=3/20) PASI 90 and 37.5% (n=3/8) of them had a significant improvement in quality of life. Non-serious adverse events were observed in 65.2% (n=15/23) of patients (diarrhoea in 39%), resulting in discontinuation of treatment for 27.8%. The average duration of treatment was 303.8±252.4 days. For four patients, a recurrence or a progression of cancer was recorded during APR treatment. CONCLUSION: In our patients with both psoriasis and cancer, APR improved quality of life, with a good safety profile. A larger study, matched for type, stage and treatment of underlying cancer, would be necessary to draw further conclusions about the oncological safety of APR.
Assuntos
Psoríase , Qualidade de Vida , Humanos , Estudos Retrospectivos , Talidomida/efeitos adversos , Psoríase/complicações , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , Índice de Gravidade de Doença , Resultado do Tratamento , Anti-Inflamatórios não Esteroides/uso terapêuticoAssuntos
Predisposição Genética para Doença , Receptor Celular 2 do Vírus da Hepatite A/genética , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/genética , Linfoma de Células T/diagnóstico , Linfoma de Células T/genética , Mutação , Paniculite/diagnóstico , Paniculite/genética , Biomarcadores , Feminino , Estudos de Associação Genética , Humanos , MasculinoRESUMO
BACKGROUND: Dupilumab is the first biologic available to treat atopic dermatitis (AD). Its effectiveness and safety were demonstrated in clinical trials. OBJECTIVE: We sought to assess the effectiveness and safety of dupilumab in adults with AD in a real-life French multicenter retrospective cohort. METHODS: We included patients treated during March 2017-April 2018. Efficacy outcomes, including Scoring Atopic Dermatitis (SCORAD) and Eczema Area and Severity Index (EASI) scores, were collected at baseline and 3 months when available. Adverse events (AEs) were recorded at follow-up. RESULTS: We included 241 patients. The median ± interquartile range (IQR) follow-up time was 3.8 ± 3.7 months. A ≥75% improvement in SCORAD was achieved in 27 of 163 (16.6%) patients, and a ≥75% improvement in EASI was achieved in 40 of 82 (48.8%) patients. The median SCORAD and EASI scores at 3 months were significantly lower than those at baseline (SCORAD ± IQR, 25 ± 21 vs 56 ± 27.4, P < 10-9 and EASI ± IQR, 4.1 ± 6.8 vs 17.9 ± 15.4, P < 10-9, respectively). Conjunctivitis was reported in 84 of 241 (38.2%) patients. The proportion with eosinophilia (>500 cells/mm3) during follow-up (57%) was higher than that at baseline (33.7%) (n = 172, P < 10-6). Dupilumab was stopped in 42 cases; 27 patients stopped because of AEs. LIMITATIONS: No control group, missing data. CONCLUSION: This real-life study demonstrated a similar dupilumab effectiveness as that seen in clinical trials, but it also revealed a higher frequency of conjunctivitis and eosinophilia.
